Exhaled biomarkers and gene expression at preschool age improve asthma prediction at 6 years of age.

RATIONALE: A reliable asthma diagnosis is difficult in wheezing preschool children. OBJECTIVES: To assess whether exhaled biomarkers, expression of inflammation genes, and early lung function measurements can improve a reliable asthma prediction in preschool wheezing children. METHODS: Two hundred two preschool recurrent wheezers (aged 2-4 yr) were prospectively followed up until 6 years of age. At 6 years of age, a diagnosis (asthma or transient wheeze) was based on symptoms, lung function, and asthma medication use. The added predictive value (area under the receiver operating characteristic curve [AUC]) of biomarkers to clinical information (assessed with the Asthma Predictive Index [API]) assessed at preschool age in diagnosing asthma at 6 years of age was determined with a validation set. Biomarkers in exhaled breath condensate, exhaled volatile organic compounds (VOCs), gene expression, and airway resistance were measured. MEASUREMENTS AND MAIN RESULTS: At 6 years of age, 198 children were diagnosed (76 with asthma, 122 with transient wheeze). Information on exhaled VOCs significantly improved asthma prediction (AUC, 89% [increase of 28%]; positive predictive value [PPV]/negative predictive value [NPV], 82/83%), which persisted in the validation set. Information on gene expression of toll-like receptor 4, catalase, and tumor necrosis factor-α significantly improved asthma prediction (AUC, 75% [increase of 17%]; PPV/NPV, 76/73%). This could not be confirmed after validation. Biomarkers in exhaled breath condensate and airway resistance (pre- and post- bronchodilator) did not improve an asthma prediction. The combined model with VOCs, gene expression, and API had an AUC of 95% (PPV/NPV, 90/89%). CONCLUSIONS: Adding information on exhaled VOCs and possibly expression of inflammation genes to the API significantly improves an accurate asthma diagnosis in preschool children. Clinical trial registered with www.clinicaltrial.gov (NCT 00422747).

Associations between asthma, overweight and physical activity in children: a cross-sectional study.

BACKGROUND: Asthma and obesity are highly prevalent in children, and are interrelated resulting in a difficult-to-treat asthma-obesity phenotype. The exact underlying mechanisms of this phenotype remain unclear, but decreased physical activity (PA) could be an important lifestyle factor. We hypothesize that both asthma and overweight/obesity decrease PA levels and interact on PA levels in asthmatic children with overweight/obesity. METHODS: School-aged children (n = 122) were divided in 4 groups (healthy control, asthma, overweight/obesity and asthma, and overweight/obesity). Children were asked to perform lung function tests and wear an activity monitor for 7 days. PA was determined by: step count, active time, screen time, time spent in organized sports and active transport forms. We used multiple linear regression techniques to investigate whether asthma, body mass index-standard deviation score (BMI-SDS), or the interaction term asthma x BMI-SDS were associated with PA. Additionally, we tested if asthma features (including lung function and medication) were related to PA levels in asthmatic children. RESULTS: Asthma, BMI-SDS and the interaction between asthma x BMI-SDS were not related to any of the PA variables (p ≥ 0.05). None of the asthma features could predict PA levels (p ≥ 0.05). Less than 1 in 5 children reached the recommended daily step count guidelines of 12,000 steps/day. CONCLUSION: We found no significant associations between asthma, overweight and PA levels in school-aged children in this study. However, as PA levels were worryingly low, effective PA promotion in school-aged children is necessary.

Integrative genomic analysis identifies a role for intercellular adhesion molecule 1 in childhood asthma.

BACKGROUND: Childhood asthma is characterized by chronic airway inflammation. Integrative genomic analysis of airway inflammation on genetic and protein level may help to unravel mechanisms of childhood asthma. We aimed to employ an integrative genomic approach investigating inflammation markers on DNA, mRNA, and protein level at preschool age in relationship to asthma development. METHODS: In a prospective study, 252 preschool children (202 recurrent wheezers, 50 controls) from the Asthma DEtection and Monitoring (ADEM) study were followed until the age of six. Genetic variants, mRNA expression in peripheral blood mononuclear cells, and protein levels in exhaled breath condensate for intercellular adhesion molecule 1 (ICAM1), interleukin (IL)4, IL8, IL10, IL13, and tumor necrosis factor α were analyzed at preschool age. At six years of age, a classification (healthy, transient wheeze, or asthma) was based on symptoms, lung function, and medication use. RESULTS: The ICAM1 rs5498 A allele was positively associated with asthma development (p = 0.02) and ICAM1 gene expression (p = 0.01). ICAM1 gene expression was positively associated with exhaled levels of soluble ICAM1 (p = 0.04) which in turn was positively associated with asthma development (p = 0.01). Furthermore, rs1800872 and rs1800896 in IL10 were associated with altered IL10 mRNA expression (p < 0.01). Exhaled levels of IL4, IL10, and IL13 were positively associated with asthma development (p < 0.01). CONCLUSIONS: In this unique prospective study, we demonstrated that ICAM1 is associated with asthma development on DNA, mRNA, and protein level. Thus, ICAM1 is likely to be involved in the development of childhood asthma.

Exercise training in children with asthma: a systematic review.

Exercise can provoke asthma symptoms, such as dyspnoea, in children with asthma. Exercise-induced bronchoconstriction (EIB) is prevalent in 40-90% of children with asthma. Conversely, exercise can improve physical fitness. The purpose of this paper is to provide a systematic review of the literature regarding the effects of exercise training in children with asthma, particularly in relation to: EIB, asthma control, pulmonary function, cardiorespiratory parameters and parameters of underlying pathophysiology. A systematic search in several databases was performed. Controlled trials that undertook a physical training programme in children with asthma (aged 6-18 years) were selected. Twenty-nine studies were included. Training had positive effects on several cardiorespiratory fitness parameters. A few studies demonstrated that training could improve EIB, especially in cases where there was sufficient room for improvement. Peak expiratory flow was the only lung function parameter that could be improved substantially by training. The effects of training on asthma control, airway inflammation and bronchial hyper-responsiveness were barely studied. Owing to the overall beneficial effects of training and the lack of negative effects, it can be concluded that physical exercise is safe and can be recommended in children with asthma. A training programme should have a minimum duration of 3 months, with at least two 60 min training sessions per week, and a training intensity set at the (personalised) ventilatory threshold. Further research is recommended regarding the effects of exercise on underlying pathophysiological mechanisms and asthma control in children with asthma.

Exhaled breath profiling in diagnosing wheezy preschool children.

Although wheeze is common in preschool children, the underlying pathophysiology has not yet been disentangled. Volatile organic compounds (VOCs) in exhaled breath may serve as noninvasive markers of early wheeze. We aimed to assess the feasibility of VOC collection in preschool children, and to study whether a VOC profile can differentiate between children with and without recurrent wheeze. We included children (mean (range) age 3.3 (1.9-4.5) yrs) with (n=202) and without (n=50) recurrent wheeze. Exhaled VOCs were analysed by gas chromatography-time-of-flight mass spectrometry. VOC profiles were generated by ANOVA simultaneous component analysis (ASCA) and sparse logistic regression (SLR). Exhaled breath collection was possible in 98% of the children. In total, 913 different VOCs were detected. The signal-to-noise ratio improved after correction for age, sex and season using ASCA pre-processing. An SLR model with 28 VOCs correctly classified 83% of the children (84% sensitivity, 80% specificity). After six-fold cross-validation, 73% were correctly classified (79% sensitivity, 50% specificity). Assessment of VOCs in exhaled breath is feasible in young children. VOC profiles are able to distinguish children with and without recurrent wheeze with a reasonable accuracy. This proof of principle paves the way for additional research on VOCs in preschool wheezing.

Multifactorial intervention for children with asthma and overweight (Mikado): study design of a randomised controlled trial.

BACKGROUND: In children, the prevalence's of both obesity and asthma are disconcertingly high. Asthmatic children with obesity are characterised by less asthma control and a high need for asthma medication. As the obese asthmatic child is becoming more common in the clinical setting and the disease burden of the asthma-obesity phenotype is high, there is an increasing need for effective treatment in these children. In adults, weight reduction resulted in improved lung function, better asthma control and less need for asthma medication. In children this is hardly studied. The Mikado study aims to evaluate the effectiveness of a long term multifactorial weight reduction intervention, on asthma characteristics in children with asthma and a high body weight. METHODS/DESIGN: The Mikado study is a two-armed, randomised controlled trial. In total, 104 participants will be recruited via online questionnaires, pulmonary paediatricians, the youth department of the Municipal Health Services and cohorts of existing studies. All participants will be aged 6-16 years, will have current asthma, a Body Mass Index in the overweight or obesity range, and no serious comorbidities (such as diabetes, heart diseases). Participants in the intervention arm will receive a multifactorial intervention of 18 months consisting of sessions concerning sports, parental involvement, individual counselling and lifestyle advices including dietary advices and cognitive behavioural therapy. The control group will receive usual care. The primary outcome variables will include Forced Expiratory Volume in one second and Body Mass Index - Standard Deviation Score. Secondary outcomes will include other lung function parameters (including dynamic and static lung function parameters), asthma control, asthma-specific quality of life, use of asthma medication and markers of systemic inflammation and airway inflammation. DISCUSSION: In this randomised controlled trial we will study the potential of a multifactorial weight reduction intervention to improve asthma-related outcome measures in asthmatic children with overweight. Moreover, it will provide information about the underlying mechanisms in the relationship between asthma and a high body weight in children. These findings can contribute to optimal management programs and better clinical guidelines for children with asthma and overweight. TRIAL REGISTRATION: Clinicaltrial.gov NCT00998413.

Clinical use of exhaled volatile organic compounds in pulmonary diseases: a systematic review.

There is an increasing interest in the potential of exhaled biomarkers, such as volatile organic compounds (VOCs), to improve accurate diagnoses and management decisions in pulmonary diseases. The objective of this manuscript is to systematically review the current knowledge on exhaled VOCs with respect to their potential clinical use in asthma, lung cancer, chronic obstructive pulmonary disease (COPD), cystic fibrosis (CF), and respiratory tract infections. A systematic literature search was performed in PubMed, EMBASE, Cochrane database, and reference lists of retrieved studies. Controlled, clinical, English-language studies exploring the diagnostic and monitoring value of VOCs in asthma, COPD, CF, lung cancer and respiratory tract infections were included. Data on study design, setting, participant characteristics, VOCs techniques, and outcome measures were extracted. Seventy-three studies were included, counting in total 3,952 patients and 2,973 healthy controls. The collection and analysis of exhaled VOCs is non-invasive and could be easily applied in the broad range of patients, including subjects with severe disease and children. Various research groups demonstrated that VOCs profiles could accurately distinguish patients with a pulmonary disease from healthy controls. Pulmonary diseases seem to be characterized by a disease specific breath-print, as distinct profiles were found in patients with dissimilar diseases. The heterogeneity of studies challenged the inter-laboratory comparability. In conclusion, profiles of VOCs are potentially able to accurately diagnose various pulmonary diseases. Despite these promising findings, multiple challenges such as further standardization and validation of the diverse techniques need to be mastered before VOCs can be applied into clinical practice.

Elevated inflammatory markers at preschool age precede persistent wheezing at school age.

BACKGROUND: Wheeze is a heterogeneous symptom in preschool children. At preschool age it is hard to predict whether symptoms will pass or persist and develop into asthma. Our objective is to prospectively study whether inflammatory markers in exhaled breath condensate (EBC) and pre- and post-bronchodilator interrupter resistance (Rint) assessed at preschool age, are associated with wheezing phenotypes at school age. METHODS: Children (N = 230) were recruited from the Asthma DEtection and Monitoring (ADEM) study. At preschool age [mean (SE): 3.3 (0.1) yr], pre- and post-bronchodilator Rint was assessed. EBC was collected using a closed glass condenser. Inflammatory markers (IL-2, IL-4, IL-8, IL-10, sICAM) were measured using multiplex immunoassay. Wheezing phenotypes at 5 yr of age were determined based on longitudinal assessment. Children were classified as: never (N = 47), early-transient (N = 89) or persistent wheezers (N = 94). RESULTS: Persistent wheezers had elevated levels of all interleukins at preschool age compared to children who never wheezed (p < 0.05). EBC markers did not differ between the persistent and transient wheezers. There was no marked difference in Rint between wheezing phenotypes. CONCLUSIONS: We demonstrated that 5 yr old children with persistent wheeze already had elevated exhaled inflammatory markers at preschool age compared to never wheezers, indicating augmented airway inflammation in these children.

Exhaled Breath Analysis for Investigating the Use of Inhaled Corticosteroids and Corticosteroid Responsiveness in Wheezing Preschool Children.

Exhaled breath analysis has great potential in diagnosing various respiratory and non-respiratory diseases. In this study, we investigated the influence of inhaled corticosteroids (ICS) on exhaled volatile organic compounds (VOCs) of wheezing preschool children. Furthermore, we assessed whether exhaled VOCs could predict a clinical steroid response in wheezing preschool children. We performed a crossover 8-week ICS trial, in which 147 children were included. Complete data were available for 89 children, of which 46 children were defined as steroid-responsive. Exhaled VOCs were measured by GC-tof-MS. Statistical analysis by means of Random Forest was used to investigate the effect of ICS on exhaled VOCs. A set of 20 VOCs could best discriminate between measurements before and after ICS treatment, with a sensitivity of 73% and specificity of 67% (area under ROC curve = 0.72). Most discriminative VOCs were branched C11H24, butanal, octanal, acetic acid and methylated pentane. Other VOCs predominantly included alkanes. Regularised multivariate analysis of variance (rMANOVA) was used to determine treatment response, which showed a significant effect between responders and non-responders (p < 0.01). These results show that ICS significantly altered the exhaled breath profiles of wheezing preschool children, irrespective of clinical treatment response. Furthermore, exhaled VOCs were capable of determining corticosteroid responsiveness in wheezing preschool children.

Feasibility study on exhaled-breath analysis by untargeted Selected-Ion Flow-Tube Mass Spectrometry in children with cystic fibrosis, asthma, and healthy controls: Comparison of data pretreatment and classification techniques.

Selected-Ion Flow-Tube Mass Spectrometry (SIFT-MS) has been applied in a clinical context as diagnostic tool for breath samples using target biomarkers. Exhaled breath sampling is non-invasive and therefore much more patient friendly compared to bronchoscopy, which is the golden standard for evaluating airway inflammation. In the actual pilot study, 55 exhaled breath samples of children with asthma, cystic-fibrosis and healthy individuals were included. Rather than focusing on the analysis of target biomarkers or on the identification of biomarkers, different data analysis strategies, including a variety of pretreatment, classification and discrimination techniques, are evaluated regarding their capacity to distinguish the three classes based on subtle differences in their full scan SIFT-MS spectra. Proper data-analysis strategies are required because these full scan spectra contain much external, i.e. unwanted, variation. Each SIFT-MS analysis generates three spectra resulting from ion-molecule reactions of analyte molecules with H3O+, NO+ and O2+. Models were built with Linear Discriminant Analysis, Quadratic Discriminant Analysis, Soft Independent Modelling by Class Analogy, Partial Least Squares - Discriminant Analysis, K-Nearest Neighbours, and Classification and Regression Trees. Perfect models, concerning overall sensitivity and specificity (100% for both) were found using Direct Orthogonal Signal Correction (DOSC) pretreatment. Given the uncertainty related to the classification models associated with DOSC pretreatments (i.e. good classification found also for random classes), other models are built applying other preprocessing approaches. A Partial Least Squares - Discriminant Analysis model with a combined pre-processing method considering single value imputation results in 100% sensitivity and specificity for calibration, but was less good predictive. Pareto scaling prior to Quadratic Discriminant Analysis resulted in 41/55 correctly classified samples for calibration and 34/55 for cross-validation. In future, the uncertainty with DOSC and the applicability of the promising preprocessing methods and models must be further studied applying a larger representative data set with a more extensive number of samples for each class. Nevertheless, this pilot study showed already some potential for the untargeted SIFT-MS application as a rapid pattern-recognition technique, useful in the diagnosis of clinical breath samples.

Metabolomics of volatile organic compounds in cystic fibrosis patients and controls.

In cystic fibrosis (CF), airway inflammation causes an increased production of reactive oxygen species, responsible for degradation of cell membranes. During this process, volatile organic compounds (VOCs) are formed. Measurement of VOCs in exhaled breath of CF patients may be useful for the assessment of airway inflammation. This study investigates whether "metabolomics' of VOCs could discriminate between CF and controls, and between CF patients with and without Pseudomonas colonization. One hundred five children (48 with CF, 57 controls) were included in this study. After exhaled breath collection, samples were transferred onto tubes containing active carbon to adsorb and stabilize VOCs. Samples were analyzed by gas chromatography-time of flight-mass spectrometry to assess VOC profiles. Analysis showed that 1099 VOCs had a prevalence of at least 7%. By using 22 VOCs, a 100% correct identification of CF patients and controls was possible. With 10 VOCs, 92% of the subjects were correctly classified. The reproducibility of VOC measurements with a 1-h interval was very good (match factor 0.90 +/- 0.038). We conclude that metabolomics of VOCs in exhaled breath was possible in a reproducible way. This new technique was able to discriminate not only between CF patients and controls but also between CF patients with or without Pseudomonas colonization.

The impact of interpregnancy weight change on perinatal outcomes in women and their children: A systematic review and meta-analysis.

Prepregnancy overweight and obesity are associated with higher risk of perinatal complications. However, the effect of weight change prior to pregnancy on perinatal outcome is largely unknown. Therefore, it is aimed to examine the impact on perinatal outcomes of interpregnancy BMI change in women of different BMI categories. The MEDLINE, EMBASE, LILACS, and CINAHL databases were searched (1990-August 2019). Observational studies on interpregnancy BMI change were selected. Outcomes evaluated were gestational diabetes mellitus (GDM), preeclampsia, gestational hypertension (GH), cesarean section, preterm birth, and newborns being large (LGA) or small (SGA) for gestational age. Meta-analyses and meta-regression analyses were executed. Thirty studies were included (n > 1 million). Interpregnancy BMI gain was associated with a higher risk of GDM (for BMI gain ≥3 kg/m2 : OR 2.21; [95%CI 1.53-3.19]), preeclampsia (1.77 [1.53-2.04]), GH (1.78 [1.61-1.97]), cesarean section (1.32 [1.24-1.39]), and LGA (1.54 [1.28-1.86]). The effects of BMI gain were most pronounced in women with BMI <25 kg/m2 before the first pregnancy regarding GDM, GH, and cesarean section. Except for LGA, interpregnancy BMI loss did not result in a decreased risk of perinatal complications. In this study, women of normal weight who gain weight before pregnancy were identified as a high-risk population for perinatal complications. This emphasizes that weight management is important for women of all BMI categories and a pregnancy wish.

Early diagnosis of asthma in young children by using non-invasive biomarkers of airway inflammation and early lung function measurements: study protocol of a case-control study.

BACKGROUND: Asthma is the most common chronic disease in childhood, characterized by chronic airway inflammation. There are problems with the diagnosis of asthma in young children since the majority of the children with recurrent asthma-like symptoms is symptom free at 6 years, and does not have asthma. With the conventional diagnostic tools it is not possible to differentiate between preschool children with transient symptoms and children with asthma. The analysis of biomarkers of airway inflammation in exhaled breath is a non-invasive and promising technique to diagnose asthma and monitor inflammation in young children. Moreover, relatively new lung function tests (airway resistance using the interrupter technique) have become available for young children. The primary objective of the ADEM study (Asthma DEtection and Monitoring study), is to develop a non-invasive instrument for an early asthma diagnosis in young children, using exhaled inflammatory markers and early lung function measurements. In addition, aetiological factors, including gene polymorphisms and gene expression profiles, in relation to the development of asthma are studied. METHODS/DESIGN: A prospective case-control study is started in 200 children with recurrent respiratory symptoms and 50 control subjects without respiratory symptoms. At 6 years, a definite diagnosis of asthma is made (primary outcome measure) on basis of lung function assessments and current respiratory symptoms ('golden standard'). From inclusion until the definite asthma diagnosis, repeated measurements of lung function tests and inflammatory markers in exhaled breath (condensate), blood and faeces are performed. The study is registered and ethically approved. DISCUSSION: This article describes the study protocol of the ADEM study. The new diagnostic techniques applied in this study could make an early diagnosis of asthma possible. An early and reliable asthma diagnosis at 2-3 years will have consequences for the management of the large group of young children with asthma-like symptoms. It will avoid both over-treatment of children with transient wheeze and under-treatment of children with asthma. This might have a beneficial influence on the prognosis of asthma in these young children. Besides, insight into the pathophysiology and aetiology of asthma will be obtained. TRIAL REGISTRATION: This study is registered by (ClinicalTrials.gov) (NCT00422747).

Feasibility and diagnostic accuracy of an electronic nose in children with asthma and cystic fibrosis.

The measurement of volatile organic compounds (VOCs) in exhaled breath is a promising tool for diagnosing and monitoring various lung diseases in children. Gas chromatography mass spectrometry (GC-MS) analysis is a frequently used standard technique for VOCs analysis. However, as GC-MS is an expensive and time-consuming technique, hand-held devices or electronic noses have been developed. Recently, the Aeonose was introduced as an easy-to-use hand-held eNose capable of point-of-care testing. Although first results using this eNose in adults are promising, studies in children are lacking. We therefore performed a cross-sectional study in 55 children and adolescents ≥6 years of age (20 children with moderate to severe asthma, 13 children with CF, and 22 healthy controls). The feasibility of the Aeonose was high (>98% successful measurements). The diagnostic accuracy was high for discriminating asthma from CF (Area Under the Receiver Operating Characteristic Curve [AUC] 0.90 [95% Confidence Interval 0.78-1.00] sensitivity 89% [65%-98%], specificity 77% [46%-94%]), and for the distinction between CF and healthy controls (AUC 0.87 [0.74-1.00], sensitivity 85% [54%-97%], specificity 77% [54%-91%]). However, the diagnostic accuracy for the discrimination between asthma and healthy controls was modest (AUC 0.79 [0.63-0.94], sensitivity 74% [49%-90%], specificity 91% [69%-98%]). This is the first study to report test results of the Aeonose in children and adolescents ≥6 years. This eNose showed a high feasibility with modest to good diagnostic accuracies in asthma and CF. This study was registered at clinicaltrial.gov (NCT03377686).

Towards Prepared mums (TOP-mums) for a healthy start, a lifestyle intervention for women with overweight and a child wish: study protocol for a randomised controlled trial in the Netherlands.

INTRODUCTION: Periconception obesity is associated with a higher risk for adverse perinatal outcomes such as gestational diabetes mellitus, preeclampsia, large for gestational age, operative delivery and preterm birth. Lifestyle interventions during pregnancy have resulted in insufficient effects on reducing these perinatal complications. A few reasons for this disappointing effect can be suggested: (1) the time period during pregnancy for improvement of developmental circumstances is too short; (2) the periconception period in which complications originate is not included; and (3) lifestyle interventions may not have been sufficiently multidisciplinary and customised. A preconception lifestyle intervention might be more effective to reduce perinatal complications. Therefore, the aim of the Towards Prepared mums study is to evaluate the effect of a lifestyle intervention starting prior to conception on lifestyle behaviour change. METHODS AND ANALYSIS: This protocol outlines a non-blinded, randomised controlled trial. One hundred and twelve women (18-40 years of age) with overweight or obesity (body mass index≥25.0 kg/m2) who plan to conceive within 1 year will be randomised to either the intervention or care as usual group. The intervention group will receive a multidisciplinary, customised lifestyle intervention stimulating physical activity, a healthy diet and smoking cessation, if applicable. The lifestyle intervention and monitoring will take place until 12 months postpartum. The primary outcome is difference in weight in kg from baseline to 6 weeks postpartum. Secondary outcomes are gestational weight gain, postpartum weight retention, smoking cessation, dietary and physical activity habits. Furthermore, exploratory outcomes include body composition, cardiometabolic alterations, time to pregnancy, need for assisted reproductive technologies, perinatal complications of mother and child, and lung function of the child. Vaginal and oral swabs, samples of faeces, breast milk, placenta and cord blood will be stored for evaluation of microbial flora, epigenetic markers and breast milk composition. Furthermore, a cost-effectiveness analysis will take place. ETHICS AND DISSEMINATION: Ethical approval was obtained from the Medical Ethical Committee of Maastricht University Medical Centre+ (NL52452.068.15/METC152026). Knowledge derived from this study will be made available by publications in international peer-reviewed scientific journals and will be presented at (inter)national scientific conferences. A dissemination plan for regional and national implementation of the intervention is developed. TRIAL REGISTRATION NUMBER: ClinicalTrials.gov NCT02703753.

Correction: A Multifactorial Weight Reduction Programme for Children with Overweight and Asthma: A Randomized Controlled Trial.

[This corrects the article DOI: 10.1371/journal.pone.0157158.].

The effect of body weight on distal airway function and airway inflammation.

BACKGROUND/OBJECTIVES: Obesity is a global health problem that adversely influences the respiratory system. We assessed the effects of body mass index (BMI) on distal airway function and airway inflammation. SUBJECTS/METHODS: Impulse oscillometry (IOS) as a measure of distal airway function, together with spirometry, were assessed in adults with a range of different BMIs. Airway inflammation was assessed with the fraction of exhaled nitric oxide (FeNO) and participants exhaled at various exhalation flows to determine alveolar and bronchial NO. RESULTS: In total 34 subjects were enrolled in the study; 19 subjects had a normal BMI (18.50-24.99), whilst 15 subjects were overweight (BMI 25.00-29.99), or obese (BMI ≥30). All subjects had normal spirometry. However, IOS measures of airway resistance (R) at 5Hz, 20Hz and frequency dependence (R5-20) were elevated in overweight/obese individuals, compared to subjects with a normal BMI (median (interquartile range)); 5Hz: 0.41 (0.37, 0.45) vs. 0.32 (0.30, 0.37)kPa/l/s; 20Hz: 0.34 (0.30, 0.37) vs. 0.30 (0.26, 0.33)kPa/l/s; R5-20: 0.06 (0.04, 0.11) vs. 0.03 (0.01, 0.05)kPa/l/s; p<0.05), whereas airway reactance at 20Hz was decreased in overweight/obese individuals (20Hz: 0.07 (0.03, 0.09) vs. 0.10 (0.07, 0.13)kPa/l/s, p=0.009; 5Hz: -0.12 (-0.15, -0.10) vs. -0.10 (-0.13, -0.09)kPa/l/s, p=0.07). In contrast, within-breath IOS measures (a sign of expiratory flow limitation) and FeNO inflammatory measures, did not differ between groups (p>0.05). CONCLUSIONS: Being overweight has significant effects on distal and central airway function as determined by IOS, which is not detected by spirometry. Obesity does not influence airway inflammation as measured by FeNO. IOS is a reliable technique to identify airway abnormalities in the presence of normal spirometry in overweight people.